Interstitial pulmonary fibrosis involves a net increase in lung collagen. A model of interstitial pulmonary fibrosis produced by instilling bleomycin into the tracheas of hamsters shares many of the histologic, physiologic and biochemical features of the human disease. In preliminary studies, we have observed that hamster pulmonary macrophages release collagenolytic activity into cell culture medium. Further, freezing of pulmonary macrophages lysates releases collagenolytic activity not otherwise detectable. We propose to develop techniques for maximal activation of collagenolytic activity, using freezing, hypo- and hypertonic solutions, detergents, and protein-denaturing agents. We will attempt to determine whether pulmonary macrophages in monolayer culture secrete preformed or newly synthesized enzyme. We will purify pulmonary macrophage collagenase by salt fractionation and various chromatographic procedures. Partial characterization of purified pulmonary macrophage collagenase will include the determination of molecular weight, isoelectric point, inhibitor profile and the nature of collagen degradation products. We will attempt to develop an antibody to purified collagenase. Our overall goal is to study pulmonary macrophage collagenase production in bleomycin-induced pulmonary fibrosis in hamsters. We wish to determine whether pulmonary macrophages from fibrotic hamsters contain more collagenolytic activity than normals; we wish to compare lavageable (airways and alveolar) pulmonary macrophages with interstitial pulmonary macrophages and lastly, we wish to relate pulmonary macrophage collagenase content or production to collagen levels at different time points in the evolution of bleomycin-induced pulmonary fibrosis. We hope that our work will help provide a basis for experimental therapeutic intervention in interstitial pulmonary fibrosis, since clinical attempts to reduce collagen synthesis have met with little success.